This blog provides news and commentary on public policy, business and economic issues related to the $3 billion California stem cell agency, officially known as the California Institute for Regenerative Medicine(CIRM). David Jensen, a retired California newsman, has published this blog since January 2005. His email address is djensen@californiastemcellreport.com.

Monday, September 30, 2013

Directors of the $3 billion California stem cell agency meet next
week to consider changes in conflict of interest rules for the
persons who make virtually all the decisions on the hundreds of
applications for the cash that it hands out for research.

Details of the changes and their justification are not yet
publicly available for the meeting in Burlingame, Ca., on Oct. 9. The
only information that was posted on the CIRM Web site as of this
morning was this brief note from the meeting agenda:

“Request for consent to initiate rule-making to amend conflict
of interest regulations for non-ICOC members of the Grants Working
Group.”

ICOC is the abbreviation for the stem cell governing board,
whose members are required to publicly disclose many of their
financial interests.

The changes would affect the out-of-state scientists who score
grant applications during closed-door deliberations. The agency's
governing board, which has the ultimate legal authority for
application approval, has ratified 98 percent of the decisions by the
grant working group, according to the agency's own calculations.

The agency does not require the scientists to disclose publicly
either their economic or professional interests and has resisted
proposals for more transparency for years. The interests of
reviewers instead are disclosed privately to a limited number of
persons within the agency There does not appear to be a significant
effort to audit the disclosures for accuracy.

Questions about the legal necessity for public disclosure of grant
reviewers' interests have arisen as far back as 2007, including a recommendation by the state auditor that the agency seek an opinion
from the state attorney general on the matter. The auditor said,

“The
FPPC (the state's government ethics agency) believes that members of
working groups, who perform duties such as advising the committee on
standards and policy or evaluating grant applications and making
award recommendations to the committee, may need to be included in
the conflict-of-interest code. Specifically, the FPPC believes that,
under state regulations, working group members may act as decision
makers if they make substantive recommendations that are, over an
extended period, regularly approved without significant amendment or
modification by the committee. Thus, as decision makers, working
group members would need to be subject to the conflict-of-interest
code.”

“The recommendations of
the CIRM working groups have never been routinely and/or regularly
adopted by the ICOC. Until the time that such a pattern is detected,
the question you suggest we raise with the attorney general is
entirely hypothetical, and is therefore not appropriate for
submission. We will, however, continue to monitor approvals for such
a pattern and will reconsider our decision if one emerges."

Because of the closed door nature of the grant application review
process, conflict questions rarely surface publicly. Last spring,
however, the California Stem Cell Report reported conflict violations involving an internationally reknown scientist-reviewer in a $40
million grant round. The scientist, Lee Hood of Seattle, Wash., is a
close friend of one of the applicants, Irv Weissman of Stanford. They
also own property together in Montana.

As we reported at the time,

“The conflict was not discovered by
the agency during the review. It was raised by another reviewer at
the end of the review, which, for the first time in CIRM history,
failed to conclude with a decision supporting any of the proposals.
Reviewers' comments have been sent back to applicants with another
review scheduled for November. The agency said Hood will not take
part in that session.”

Hood was recruited as a reviewer by CIRM President Alan Trounson,
who has been a guest of Weissman at the Hood-Weissman ranch.
Sphere: Related Content

The $3 billion California stem cell agency is predicting that
“human healthcare will be greatly improved” by stem cell research
by 2024 and this week is fleshing out some of the details of an
ambitious plan to help make that happen.

The staff document said a workshop earlier this year developed a
“consensus that it would be beneficial if the CIRM (the stem cell
agency) regulations reflected existing state and federal requirements
with regard to delegation of responsibility and avoid unnecessary
duplication of effort, such as the IRB (institutional review board)
responsibility for the risk and benefit assessment.”

The staff is recommending that “CIRM’s regulatory requirements
for clinical research should be modified to avoid duplication of
IRB’s responsibility for review and approval of clinical trials.”

The staff also said,

“CIRM’s existing regulatory requirements for notification,
review and approval of basic and pre-clinical research appear
effective at this time without creating undue burdens. In fact,
mature systems appear to be in place to efficiently incorporate ESCRO
(embryonic stem cell research oversight) operations into
institutional compliance programs.”

Also on the standards group agenda are issues dealing with
informed consent by providers of somatic cells “obtained under
general (biomedical) research protocols" in connection with iPSC (induced
pluripotent stem cell) derivation.

Dubbed the “Discuss Project,” its goal is “to initiate a
process designed to develop consensus for the use of previously
collected specimens for iPSC research" and to publish "final
considerations" in early 2014.

Another item on the agenda tomorrow involves an update on the
“progress of CIRM iPSC bank and donor consent protocol.”
Sphere: Related Content

Tuesday, September 24, 2013

Only six more days remain to submit nominations for the Stem Cell
Person of the Year.

This is the contest run by UC Davis stem cell researcher Paul
Knoepfler, who will give the winner $1,000 of his own, personal cash.

The criteria are nearly wide open although Knoepfler is looking
for the “most influential” person in the field. He wrote on his blog,

“Nominees can be almost anyone ranging from an advocate to an
academic or industry scientist to a stem cell biotech leader to a
policy maker to a physician…think outside the box! Surprise me!”

Knoepfler initiated the contest last year. The 2012 winner was Roman Reed, a San Francisco Bay Area
patient advocate.

Knoepfler reported today on his blog that he has received two
dozen nominations so far. He is planning on opening up the selection
of the semi-finalists to online voting from the list that will be
published in early October. Last year he selected the semi-finalists
himself.

As for the names he has received so far, Knoepfler said,

“This group of nominees is very diverse, far more so than last
year, and includes more scientists and physicians.”

Wednesday, September 18, 2013

The next new member of the governing board of the California stem
cell agency is likely to be a surgeon from Johns Hopkins, Julie
Freischlag.

Freischlag was named this week as the new vice chancellor for human health services and dean of the UC Davis
medical school, replacing Claire Pomeroy, who resigned to become
president of the Lasker Foundation.

Pomeroy had served on the stem cell board since 2005. She was
named to the board by the UC Davis chancellor because of her position
as dean of the medical school.

Freischlag, who is scheduled to begin her new job Feb. 10, is no
ordinary surgeon. Currently she is chair of the Department of
Surgery at Johns Hopkins. Prior to that she was chief of vascular
surgery at UCLA. A Baltimore Sunprofile of her in 2003 said she
stands out because of her stellar career in “perhaps the most macho
specialty in medicine.” The article said women surgeons are
outnumbered 5 to 1 by men.

Responding to a query from the California Stem Cell Report, a
spokeswoman for the UC Davis chancellor was noncommital about whether
Freischlag would be appointed to the stem cell agency board. Luanne
Lawrence, associate chancellor for strategic communications at Davis,
said,

“This is one of the important and transitional decisions that
hasn’t been addressed quite yet.”

However, the deans of the other major California medical schools
sit on the stem cell agency board, which gives away $300 million a
year for research. Given that context, it would seem prudent for the
dean of the UC Davis medical school to serve on the board as well.

Below is a copy of the article, which appeared on the main page of
The Bee Web site early today and which was written by yours truly. In
the print version of The Bee, the Knoepfler piece appeared on the
same page as a New York Times story dealing with dubious stem cell
treatments(Here is a link to the original version of the Times'
piece.).

The Knoepfler story was also the No. 1 article that turned up this
afternoon when the Google news category was searched using the term
“stem cell.” It is likely to be published elsewhere in the coming
weeks as it is circulated by the McClatchy News Service.

By
David Jensen

Bee
correspondent

PUBLISHED
SUNDAY, SEP. 15, 2013

In
his day job, UC Davis scientist Paul Knoepfler probes the inner
workings of stem cells and cancer cells and what makes them behave
the way they do.

On
the side, the father of three daughters blogs about costly, unproven
stem cell treatments and provides guidance for those seeking
experimental therapies.

Knoepfler
is a rare stem cell researcher who regularly explores the most
problematic aspects of stem cell therapies on the Internet in full
public gaze. He considers himself an advocate for patients as well
as a scientist, having survived an aggressive form of prostate
cancer at the age of 42.

Now
46, Knoepfler began his blog in 2010, shortly after his cancer was
diagnosed. His blogging has encountered resistance from some
colleagues, who are uncomfortable with such public endeavors. But he
has polished and expanded the blog to the point that it has received
international recognition. He will receive an award in December at
the World Stem Cell Summit in San Diego for his advocacy efforts.

This
month he moved beyond cyberspace and published “Stem Cells: An
Insider’s Guide” (World Scientific Publishing). The book covers
stem cells from A to Z and is aimed at the general reader,
especially people considering stem cell therapy for themselves, a
family member or friend.

The
book comes during what has been described by Christopher Scott, a
senior research scholar at Stanford University, as “an epidemic of
transplant clinics offering so-called cures and therapies” both
here and abroad. The international stem cell medical tourism
business, widely promoted on the Internet, is taking in roughly $1
billion annually, according to an estimate in Stanford Medicine, a
publication of the Stanford medical school.

Knoepfler
is a believer in the potential and power of stem cells. But he says
that some of the dubious stem cell treatments now being offered have
resulted in deaths and injuries. Other unpleasant issues arise as
well in stem cell research, including the tendency of some stem
cells to generate cancer cells, and Knoepfler wants to talk about
them.

“Too
often in the academic section of the stem cell field, people
pussyfoot around the most important issues or do not even dare talk
about them at all,” says Knoepfler.

He
is “not on some crusade to dissuade people from getting risky stem
cell procedures,” but says safety and training need to be
encouraged. Reckless behavior endangers the entire field, he says.

“There
is no better illustration of the risks of unlicensed stem cell
treatments administered by untrained doctors than the recently
reported case of a woman who received a stem cell facelift, only to
have bone grow in her eye,” he said, referring to a Scientific
American report involving a Beverly Hills clinic.

To
help patients, Knoepfler’s book begins with the basics: What are
stem cells? He moves on to topics ranging from whether stem cells
can treat baldness to whether they can help with afflictions such as
Alzheimer’s, autism and arthritis. Along the way, he discusses the
potential for regenerating limbs, made-to-order organ transplants
and curing spinal paralysis, none of which have reached the stage
where patients can be assured of using the techniques safely and
effectively.

Stem
cell treatments are not exactly new. They were first used in the
1950s in bone marrow transplants. More recently, what has excited
researchers and the public are pluripotent stem cells, which have
the ability to transform themselves into any part of the body. The
full range of stem cells, however, includes adult, fetal, embryonic
and induced pluripotent cells (iPS), which are also known as
reprogrammed adult stem cells.

“Each
type of stem cell has clinical promise for specific diseases, but
also certain weaknesses. Some stem cells also stir controversy. For
example, embryonic stem cells have been at the center of ethical
debates for more than a dozen years,” Knoepfler writes.

Embryonic
stem cells are derived from an embryo only a few days after
fertilization and require destruction of the embryo. It was that
type of process that triggered the federal restrictions – now
rescinded by President Barack Obama – on federal funding of
research using human embryonic stem cells. Some people believe that
the process amounts to killing a human being, while others do not.

Knoepfler
has come up with a battery of questions and “rights” that
persons considering a stem cell treatment should address as they
contemplate spending tens of thousands of dollars for treatments.

His
“patient bill of rights” includes the right to treatment by a
trained provider, the right to continuing follow-up and the right
not to be charged to participate in a clinical trial.

Just
this month, he added on his blog, ipscell.com, the top 10 questions
that patients should ask. They include such areas as the details of
the methods to be used and costs, the cell numbers and types,
regulatory compliance by the provider, data supporting the cellular
product’s effectiveness and data supporting its safety.

As
for mainstream media reports and research papers that seem to
promise miraculous cures, Knoepler says, “My advice to patients is
to be cautious when reading papers on the clinical use of stem
cells. Do not believe everything you read and avoid placing too much
weight on any one paper. If something is real, it should be
reproducible by multiple groups.”

One
of the areas of Knoepfler’s research involves cancer stem cells, a
topic of special interest to him because of his own encounter with
the disease. “Even with something as wonderful as stem cells,
there also can too much of a good thing. Stem cells can cause cancer
and in certain conditions they can make cancer especially hard to
cure,” he explains.

In
the case of embryonic stem cells, he cites their ability to form an
unusual tumor called a teratoma. Knoepfler, who was an English
literature major as an undergraduate, says, “The name ‘teratoma‘
literally means ‘monster tumor,’ and there is good reason for
that nomenclature. These tumors look monstrous when observed by eye,
akin to an animal put into a developmental blender.”

Knoepfler
did not use stem cell therapy to treat his cancer, but he says that
as a cancer survivor he understands all too well why patients turn
to it when they’re dealing with a life-threatening or
life-changing medical condition.

“If
you feel that your disease has put you in a place for which patience
is not an option,” he says, “talk with your physician. Get
second and maybe even third and fourth opinions before deciding
whether or not to proceed.”

Knoepfler’s
advice may not be appreciated by some of the firms he writes about,
but others think well of him.

Jonathan
Thomas, chairman of the $3 billion California stem cell agency, says
the field needs more scientists like Knoepfler.

“It's
hard to overstate the value of what Paul does,” Thomas said in an
email.“Paul
is a powerful advocate for helping the public understand what
research is being done, and why it is important. He is gifted at
taking complex science and turning it into plain English so that
anyone can understand what he's talking about.”

Knoepfler
has received $2.2 million from the stem cell agency for his
research, which is also funded by the federal government and other
sources. He has been at UC Davis since 2006, part of the campus’
stem cell program, which has received $131 million in grants from
the state stem cell agency since 2005, generating 333
research-related jobs.

Knoepfler,
whose father was a physician and mother a counselor, sees a bright
future for stem cells, indeed a “medical revolution.”

“Stem
cells are today’s new frontier of medicine that will no doubt have
an unimaginable impact on our lives, but even more so on the lives
of many of our kids and grandchildren,” he said.

Jensen
is a retired Sacramento Bee journalist and has produced the
California Stem Cell Report (californiastemcellreport.blogspot.com)
on the Internet since 2005, writing nearly 3,600 items.

Friday, September 13, 2013

All stem cell research is not created equal, a truism that
found fresh validity this week. Particularly research that could play a role
in whether the California stem cell agency can find more cash to continue its
operations.

The difference was highlighted yesterday by articles on the stem
cell agency’s blog. The pieces dealt with findings – some esoteric and some
not-so-esoteric -- that received international attention. The articles written by CIRM staffers Amy Adams and Don Gibbons were fine as far as they went. But it is one thing to deal with the nuts and bolts of
research and another to look at it from the perspective of whether it resonates
with the public.

The research in question is from Spain and Stanford. Researchers
in Spain reprogrammed adult cells in a
living mouse to become like embryonic stem cells. Those results received much “gee
whiz” attention in the mainstream media, most of which overlooked problematic aspects involving its cancer-linked results(see researcher Paul Knoepfler's take here and Gibbons' item here).

The other findings out of Stanford dealt with people and
Down syndrome, along with cognitive function, aging and Alzheimer’s.

"'Conceptually, this study suggests that drug-based
strategies to slow the rate of stem cell use could have profound effects on
cognitive function, aging and risk for Alzheimer’s disease in people with Down
syndrome,' said co-author Craig Garner, PhD,
who is the co-director of Stanford’s
Center for Research and Treatment of Down Syndrome and a professor of
psychiatry and behavioral sciences.”

Both the press release and the CIRM blog item briefly noted
that funding from CIRM helped to sustain the research. Stanford buried the information at the end of its release. CIRM mentioned it much higher in
its item.

In neither case were specific funding figures mentioned. Nor
was there any attempt to say whether this research would have been slow in
coming or not coming at all without CIRM help.

Why does that matter? The $3 billion state stem cell agency
will run out of funds for new grants in about three years, not very long given the
length of time it takes to develop major funding sources and the rather
deliberate pace at which CIRM works on some matters.

Currently the agency spends about $300 million year on
research and is not likely to be able to renew its funding at that level. But
if it wants to play at even the $50 million level, it will have to generate
some sizzle from the research that it has funded.

Sizzle is what the Stanford research has. It resonates with
people. We all know somebody or a family with issues such Alzheimer’s, Down
syndrome or cognitive problems. Missing largely, however, from the press releases, media
stories and even the CIRM blog is some sort of way of assessing whether CIRM
funding played a KEY role.

And that is the clincher for agency. That is the sizzle that
will sell the agency as absolutely necessary if it truly wishes to turn
stem cells into cures.

(Editor's note: Shortly after this item was posted, we searched the
agency's Web site. One of the results disclosed that agency gave $1.4
million to Michael Clarke of Stanford for the research. He has filed two progress reports on his findings.) The research received additional support from CIRM as well, but the amounts were not readily apparent.)

The California stem cell agency has re-organized its
cyberspace book shelves to help make its Web site easier to
navigate.

Nothing has been removed, said Amy Adams, the major domo
for the CIRM’s Internet operation.

Writing on the agency’s blog, she explained one of the major
changes dealing with “our funding” category.

“It turns out that people looking for information about
research we've funded weren't thinking to look under 'our funding.'
And since no other section of the site seemed like a likely place to find that
content, people sent me helpful emails suggesting that I add pages about where
our funding has gone (I politely directed them to that content).”

Most of the information on funding has now been moved to “our
progress,” she said, leaving only information on how to get and manage grants under the “our
funding” category. Other changes have occurred as well. You can read all about them here.

Wednesday, September 11, 2013

The
California stem cell agency has taken notice of a piece in the New York Times
that reports on questionable practices of enterprises that say they are stem
cell clinics.

In a blog item written yesterday by Don Gibbons, senior
science and education officer at the agency, the agency said that the practices described in the article generated a cautionary advisory to patients last month by the stem cell agency and 12 other organizations.

Gibbons noted that much
of the Sept. 9 Times article by Laura Beil focused on one clinic,the Regenerative Medicine Institute in
Tijuana, which is just on the California-Mexico border. Gibbons’ item reported that
one U.S. expert says that some of the clinic’s key procedures would not pass
muster in this country.

Gibbons continued,

“Most important, the
clinic has not produced any publishable data. We all have great hope for the
promise of stem cell science, but I think it is fair to say that anyone who
legitimately cares about that promise wants to find out what is the right type
of cell to put in each patient. When is the right time for the transplant, and
what is the best method of delivering the cells. We will never learn those
things without collecting data in a well-designed clinical trial and sharing
that data.”

“There is absolutely no
legitimate reason for such clinics to be not publishing their data.”

Gibbons also said that
the International Society for Stem Cell Research, which backed away under threats of lawsuits a few years
ago from some criticism of dubious stem cell clinics,
plans to release this week a new statement on these sorts of treatments.

We should note that
Times article, which is syndicated to many newspapers in this country, did not pick
up the widely reported instances of deaths and injuries from these treatments. It
did report that problems exist in this country as well as abroad. The article
said,

“In the United States, too, it is easy to conduct business outside government oversight, said Dr. George Q. Daley, who studies stem cells for blood diseases at Harvard Medical School. Close down one shady operation, he went on, and more seem to randomly pop up.

“Even questionable publicity does not necessarily hurt business. Regnocyte, a company in Florida, posted an unflattering CNN report about it on its Web site under the heading ‘special coverage.’”

Monday, September 09, 2013

The old saying has it that you can tell the pioneers
by the arrows in their backs.

Tell that to Paul Knoepfler, the UC Davis stem cell
researcher who has been something of a pioneer in stem cell blogging and still
is -- at least given that almost no other stem cell researcher blogs both as a researcher
and patient advocate in addition to taking on wide-ranging business and public policy
issues.

Knoepfler does have a few arrows in his back, some
from enterprises that are less than happy with his vieww of their conduct and
some from within the stem cell research community itself. But overall he has
found the experience beneficial and rewarding.

In an article in Nature Medicine Sept. 6, Knoepfler
is recruiting more researchers for the stem cell blog brigade. To encourage
them, he recounts his experiences and costs (such as $1,500 for his special
domain name, although a normal domain name can be had for virtually no cost). His
experiences include working late at night and on weekends. We can testify that
the father of three puts in the hours, just based on the nature of the
blog content and frequency of posting.

Knoepfler continues his pitch in his piece in
Nature, which is read primarily by researchers,

“To all this a reader might say, ‘Okay, this all sounds well and good, but
you can't have your cake and eat it, too! Your science must have suffered from
all this.’ In fact, I have lost some sleep, but I have not seen much in the way
of negative scientific consequences. My lab has done very well during the past
three years, and we have published many important papers, including one earlier
this year that demonstrated the molecular similarities between induced
pluripotency in stem cells and oncogenic transformation in cancer cells.
I even secured tenure during this time.

“Reflecting on my personal transformation to the role of scientist−advocate,
I have come to notice many tangible positive outcomes. In a general sense, my
work has served to build bridges and stimulate new dialogue between industry
and academia in the stem cell field. At the same time, I couple these efforts
to accountability. Today, if someone does an Internet search for 'stem cell
blog', that person will find my site, with all its educational outreach
resources, at the top of the results list. A few years ago, the same search
would mostly have yielded sites published by opponents of stem cell research or
proponents of sketchy, for-profit endeavors to attract stem cell 'tourism'. I
have also interacted with more than 100 patients and caregivers, helping them
make more educated and, I believe, safer, stem cell−related medical decisions
with their physicians.”

Knoepfler’s bottom line pitch? Any scientist can!

As he put it:

“Any scientist can, and should, do it. It is only logical that scientists
would adapt to today's reality—a funding-poor environment that is nonetheless
rich with opportunities for communication—by becoming advocates. I predict that
any scientist who devotes a tiny bit of time to advocacy endeavors will find
that the payoff is greatly multiplied. I will even help. Drop me an e-mail. Or
better yet, leave a comment on my blog or message me on Twitter. Let's get the
conversation going.”

Tuesday, September 03, 2013

The battle over whether excessive protection of stem
cell IP stifles research that can lead to cures was engaged once more today
with a broadside against the powerful Wisconsin Alumni Research Foundation(WARF).

The attack came from California’s Consumer Watchdog
organization and New York’s Public Patent Foundation which have been tussling
with WARF for seven years. The dispute over
intellectual property (IP) centers on a patent on human embryonic stem cells
held by WARF and which the other organizations are challenging in a federal
appellate court in Washington, D.C.

More specifically, the patent involves research by
Jamie Thomson of the University of Wisconsin, and now also of UC Santa Barbara,
in which he isolated human embryonic stem cells.

Consumer Watchdog of Santa Monica, Ca., this morning
issued a news release concerning the organizations’ appellate brief that was filed last
week. It cited the U.S. Supreme Court ruling earlier this year that said genes
cannot be patented because they exist in nature. The lead attorney in that successful case, Dan
Ravicher of the Public Patent Foundation, is also handling the challenge to WARF.

The news release said that Thomson deserved credit
for being first to isolate and maintain human embryonic stem cells, but “his achievement was not the result of
his having created a patentable invention.” The brief said that the work involved
was “obvious.” One of the main reasons for Thomson’s achievement, the news
release said, was that “he had
access to human embryos and financial support that other researchers did not
have.”

The brief said,

“The
claims at issue here cover human embryonic stem (hES) cells that are not
markedly different from those in our bodies. Thus, the claims are invalid under
35 U.S.C. § 101 for covering ineligible subject matter, an issue the Court may
and, as a matter of judicial economy and public policy, should address.”

The challenge to the WARF
patent has drawn impressive support in the scientific community, including Jeanne Loring, now director of the Center for
Regenerative Medicine at The Scripps Research Institute, who was involved from
the start. In 2007, Loring wrote in Nature that she became involved in the case
because “scientists have an obligation not only to perform research but to make
sure that our research can benefit the society that supports it.”

The news release said,

“Later in the case Dr.
Alan Trounson, then of Australia’s Monash University and now president of the
California Institute for Regenerative Medicine, Dr. Douglas Melton of Harvard
and Dr. Chad Cowan of Harvard filed affidavits supporting the challenge.”

About Me

The California Stem Cell Report is the only nongovernmental website devoted solely to the $3 billion California stem cell agency. The report is published by David Jensen, who worked for 22 years for The Sacramento Bee in a variety of editing positions, including executive business editor and special projects editor. He was the primary editor on the 1992 Pulitzer Prize-winning series, "The Monkey Wars" by Deborah Blum, which dealt with opposition to research on primates. Jensen served as a press aide in the 1974 campaign and first administration of Gov. Jerry Brown. (Time served: two years and one week.) He writes from his sailboat on the west coast of Mexico with occasional visits to land. Jensen began writing about the stem cell agency in 2005, noting that it is an unprecedented effort that uniquely combines big science, big business, big academia, big politics, religion, ethics and morality as well as life and death. The California Stem Cell Report has been identified as one of the best stem cell sites on the Internet. Its readership includes the media (both mainstream and science), a wide range of academic/research institutions globally, the NIH and California policy makers.